All right, so it's great to talk to everyone today. This is, I'll just warn you, this is a lot of information rushed through in a short period of time. So don't, you might leave this talk feeling a little overwhelmed. You have access to all the slides. There's a lot of information on the slides which you can have access to. And my contact information is at the end that you can certainly reach out to me if you wanna get connected with more resources. And I've included some resources for learning more about this topic at the end. So today, so I'm Sarah Spencer. I'm an addiction medicine specialist. I also do family medicine. I work down on the Kenai Peninsula in Nelshicken, Homer right now, been in Alaska for 15 years. And I'm gonna, we're gonna talk today a little bit about utilizing buprenorphine for the treatment of chronic pain. And this education is funded by the Opioid Response Network which is a SAMHSA funded organization. It provides teaching and technical assistance to organizations and individuals. And so if your organization is needing training or technical assistance, oops, they can reach out to the, well done. They can reach out to the Opioid Response Network for that. Objectives of what we're gonna cover today, we're gonna talk about kind of identifying which patients might benefit from switching over from regular opioids to buprenorphine. We're gonna look at kind of the formulations, the doses, the pharmacology of buprenorphine and some strategies on how to start this medication in patients taking chronic opioids. I don't have any financial disclosures. I work in, I work in tribal health. I work for the Nenetleshake Traditional Council. So first of all, this talk is not, is not advocating starting buprenorphine in patients who have chronic pain who aren't otherwise taking other opioids. I think there's a lot of kind of controversy on whether there's much benefit in chronic opioid therapy. There's a lot of risks associated with it but this was really looking at that population of patients who are already on chronic opioid therapy and we're looking at considering switching them from full opioid agonist to buprenorphine as in order to kind of reduce their risks and also possibly improve some quality of life issues for those people. This is, I don't know why it says 2023. This is 2022 CDC opioid, new opioid management guidelines that came out in December 22. And so it mentions, talks a lot more about buprenorphine than previous ones did. So we see here in recommendation five which talks about tapering opioids for patients that who continuing high dose opioids the risks seem to outweigh the benefits but they're really just not able to taper down and tolerate a taper down off of their current opioids. Even if they do not have an opioid use disorder they might benefit from transitioning to buprenorphine. I'm talking about how it can be helpful for pain and a safer medication. They bring this up again in recommendation 12. Again, even without a diagnosis of opioid use disorder you can consider transitioning people to buprenorphine for pain because of it's improved safety profile. The VA came out the same time, December 2022 guidelines. I think they're actually, they're worth looking at. I think they're maybe a little bit more applicable in a lot of ways than the CDC guidelines. They have different information in them. They really focused on like they do not recommend that you start opioids for chronic pain but they say, if you are gonna use opioids for chronic pain they suggest buprenorphine as the first line opioid of choice to treat chronic pain both due to its improved safety profile and also reduce risk for misuse. So- Excuse me, Sarah, it's Kim Douglas. I have a bunch of med staff trying to get into the site and it's not working. So yeah, so do we have another link I can send them? That would be- Let me go ahead and send you the link that we have here. That's the one that I used. Oh, did you get in? Yeah, something popped up on our reminder, the link it was forwarded and I just went on it but the one you sent, it was just a webpage without any link, without any Zoom meeting. Yeah, that was true. So this is the one that just popped up on my screen. It was a forward medical ORN training. That one, I just got on right now. Okay, okay. How about, let's see, I'm gonna send it again. Okay, so Emily's sending this. Okay, how do I do that? I sent it out to everyone, Kim. Huh, you did? All right. Yeah, that's the one Robert's open, so I think we're good. Okay, good. All right, thank you. Sorry. Okay, so what sort of patients might benefit from a transition to buprenorphine? So first of all, in my opinion, anyone who wants to make that switch over who's on high-period therapy can, even if they're not at particularly high risk. But certainly patients who have a lot of risk factors, they either themselves are really motivated and want to taper down off opioids or they really need to for safety matters. Maybe they have a lot of comorbidities, maybe they're on a high-risk medication, they maybe have benzodiazepines and gut and pentanoids and other things all mixed together and we're just really worried about their risk, but they are really not able to tolerate tapering down their opioids or also maybe not really not able to engage them in that conversation, they're kind of not willing due to fear and anxiety. It may also be helpful in patients who have opioid-induced hyperalgesia. We'll talk a little bit about how buprenorphine works a little differently on the opioid receptors and it may actually improve pain control and by switching people over to buprenorphine from their other opioids. And in some cases it may reduce some side effects that people are experiencing. A lot of patients really mentioned to me when they make a switch over that they really, the things they really like is that a lot of times they feel like a cloud has been lifted off of them, like they're cognitively more clear and their mood tends to improve and they just feel like their quality of life overall, they just feel better. And of course, patients who have opioid use disorder, we're definitely gonna make sure they have access to buprenorphine. There's a lot of different formulations of buprenorphine. The main ones that you're gonna see, so the ones that are approved for chronic pain we're gonna talk about later, these are the ones for opioid use disorder as their FDA indication. So suboxone is one a lot of people know, which is this buprenorphine naloxone strip. They also make buprenorphine naloxone sublingual tablets and plain buprenorphine sublingual tablets. So these are the main, we're gonna be talking about sublingual buprenorphine. These are the formulations that we're gonna be talking about when those come up. So the pharmacology of buprenorphine, it's really unique and different than other full opioid agonists. So it is a partial agonist. So it binds very tightly, has a high affinity to the opioid receptors, has a really long half-life. So it lasts for a long time, but it's only a partial agonist. So it has, when it binds those receptors, it only partially turns them on. And in terms of at least the effects of respiratory depression and euphoria, it has what's called a sealing effect. So once you get to the higher doses, you're kind of maxing out some of the saturation and some of the effects of buprenorphine, allowing it to be significantly safer in terms of respiratory depression and also abuse potential as well. And it is an incredibly safe medication. It's essentially nearly impossible. Nothing is impossible, right? But nearly impossible for an adult to overdose on buprenorphine alone. And even in combination with other CNS depressions, buprenorphine itself causes really minimal respiratory depression, even in opioid-naive patients. So this is a study that was using, looking at opioid-naive patients and giving them single doses of up to 32 milligrams of buprenorphine in a single dose, which is much higher than even folks would take generally who have opioid use disorder. And it does not cause any clinically significant respiratory depression. So very, very safe, even in very high doses. So outside of the mu receptor activity, there are also other opioid receptors we have. So we have a Delta and a Kappa opioid receptor, and buprenorphine works differently. It works as an antagonist at these receptors. And this is some of the things that can help to actually reduce the side effects of this medication. It can work as a mild antidepressant because of its antagonism of the Kappa receptor and might reduce some of the side effects. And it's only a low affinity for the NLP receptor, which is felt to also help to limit its misuse potential and also limit the development of tolerance to this medication. And though, interestingly, although some, like the respiratory depression clearly has a ceiling effect for buprenorphine, we actually don't see that when we're looking at the analgesic effect of buprenorphine. So this is looking at two different doses of buprenorphine. There's no change. They have identical effects on their respirations. But when we look at the pain relief effects, when you double the dose, you get double the analgesic effect. So there really isn't any known ceiling effect for analgesic for buprenorphine, which really means that, you know, even if patients are on high doses of buprenorphine, when they have acute pain, we can give them more buprenorphine, and it probably will be helpful. And there's not a lot of data or studies that look at the use of buprenorphine to treat pain, but we're seeing more and more of them come out in more and more meta-analysis. Essentially, they all have come to the same conclusion that buprenorphine does appear to be at least as effective or more effective than other opioid agonists in treating pain. And interestingly, it seems to be, this is another one saying that rotating people from other full opioid agonists to buprenorphine appears to provide, appears to reduce the level of pain that people experience and is well-tolerated. This is, there's a couple of studies that are looking both at, you know, patients who don't have OUD and patients who do have OUD. And interestingly, it appears that you get better, better pain relief and more improvement of your pain relief when you're switching from, when someone who does not have OUD is switching from their full opioid agonist to buprenorphine versus someone who does have OUD who's starting on buprenorphine. They don't seem to get as much benefit of pain relief from that switch over. This is an older study, but really interesting looking at patients with very high MMEs. So the average in this patient, very small study, but the average was 550 MMEs, ranged from like 100, 200 to 550, so to over a thousand MMEs. And this was switching people over to sublingual buprenorphine on between 20 to 25, 22 to 20 milligrams of sublingual buprenorphine. The average was eight milligrams. And they had a really, a really dramatic reduction in their pain scores when they switched buprenorphine. And that was true, whether they were on lower or higher MMEs. It was also true whether they initially had very high levels if their pain was normally an eight to 10, or normally their pain was pretty well controlled. Both groups of people had significant improvement in their level of pain and improvement in their quality of life measures. This is kind of comparing, this is kind of looking at lower dose buprenorphine, so transdermal buprenorphine and buccal buprenorphine. Looking at the pain relief, we see with that appears to be similar to pain relief that we're seeing with other standard commonly used opioids. This is looking at side effect profile. This is on buccal buprenorphine. So we can kind of consider that like a medium dose when we're treating with pain. And that for almost all of the measures when compared to other opioids appears to have less side effects. But I think that also is dose dependent. Subliminal buprenorphine is a higher dose and people in high dose subliminal buprenorphine, I definitely see issues like constipation is still a major issue for those people. So these are the two FDA approved formulations of buprenorphine for chronic pain. And we're not gonna spend a lot of time talking about these. They have clear instructions in the package insert on utilizing these medications and how to start the medication. So you can follow the directions in the package insert. But these formulations are expensive. Often they are not covered by insurance. Butrans, the transdermal is covered by Medicaid. But I don't think I've ever seen an insurance that covers the buccal, the belbucca formulation actually. But they have tables that talk about how you can transition people on what dose depending on what they're currently taking. And essentially the Butrans, the transdermal is gonna be the one we have most access to for at least some insurance coverage. Although they say that you can consider it in patients who are taking up to 80 MMEs. They also in the instructions say that you should taper their patients opioids down to 30 MMEs for a week before you start this Butrans. So, and I don't know, it's hard for me to imagine taking a patient who's on 70 or 80 MMEs and just cutting them down to 30 for a week before. That sounds miserable to me. So, I think in my opinion, you know, I tend to use, you know, Butrans recommended patients who are on the lower end, you know, 50 or less switch over, you know, you've tried it on anyone who wants to have ADMMAs. This is looking at the serum drug levels that you get from the Butrans. This is their, this is in the package and sort of the medication, the 10 microgram patch. And this is in picograms per milliliter. So this is basically, they're having peak serum drug levels of 0.2, 0.15 is kind of the average for the 10. So you might say like 0.15 to 0.3 for the 10 to 20 nanograms per milliliter. Now, when you compare that to sublingual buprenorphine, this is a table that has lots of formulations on it. But an eight milligram sublingual buprenorphine will give you an average steady state of 1.2. So you compare that 0.15 to 0.3 to 1.2, the significantly higher serum drug levels and 24 milligrams a day, you're getting about three nanograms per milliliter serum drug levels. When we use high dose extended release buprenorphine, we can get up to six nanograms per milliliter. So, so the, these different dosing formulations give you different options for different serum drug levels, which can depend on, you know, what kind of level tolerance the patient currently has, what might be appropriate to switch them over for. So in generally comparing these, these two FTA approved formulations to the sublingual formulation, the transdermal is going to be a much lower total daily dose of buprenorphine, roughly 0.5 milligrams a day versus, and most insurances will pay for up to 24 milligrams a day of the sublingual. So you have a much, you can get up to much higher doses using sublingual. The FDA, the sublingual isn't approved for pain, but it's commonly used for pain and you really can use it for any, you know, there's no maximum for, you know, the number of MMEs that you can switch people over on this. It's much, much cheaper. So especially if you have someone that maybe their insurance doesn't cover and they are having to pay cash, it's much cheaper than the other formulations. And the sublingual kind of inherently has abuse deterrent formulation, which is, which is nice, especially if it falls into the wrong hands that it has naloxone in it, which isn't active unless it is misused, like injected or insulated that the naloxone might cause a withdrawal in someone who has an opioid tolerance. So there, there are a lot of advantages to the sublingual films. It's the you can cut them into little pieces, which is really nice with scissors. Sometimes the tablets kind of they're dissolving and you had to be careful with the pill cutter to cut them because they could potentially crumble when you're trying to cut them. They're really generic, widely available. They're more affordable. They're really easy to transport because they're individually wrapped. And and the, the, you know, a lot of people have questions about like, is it okay to use the sublingual buprenorphine off label? Absolutely there it's a hundred percent legal. And the only issue really comes up with insurance paying for it. That really is, is the only issue with using the sublingual buprenorphine. It's not all insurances cover sublingual buprenorphine under the diagnosis of chronic pain. Some insurances only cover the patch, which that's fine if they're on lower doses of MMEs, but when patients have higher levels of tolerance, if they're on 50 to a hundred more MMEs they're probably going to need sublingual buprenorphine in order to meet their, their tolerance and pain control needs. So you usually can get sublingual buprenorphine covered for pain. If you do a PA an appeal and kind of write a letter for medical necessity. And I just kind of kind of outline what this person's risk factors and comorbidities are, what their MMEs is. And that the clearly they can, we can reduce their the risk to their health by switching them over to the buprenorphine and almost never gets rejected. You know, if you write out a good case and now when you really have that, you can link the resources of the CDC and the VA guidelines that are specifically telling us to do this now. So it's a lot harder for the insurance companies to say, no, I'm doing, I'm finding one right now though, today I got one, I got it. I got one that I had to write a repeal letter for. This is kind of a last ditch effort. Occasionally you get a patient that they just, you know, their return to just will not cover sublingual buprenorphine for chronic pain. Some patients there's the option of giving a person a diagnosis of opioid dependence, which is F11.2 or depends withdrawal F11.23 versus the diagnosis of opioid use disorder of 11.19 that, you know, in the addiction world, we think, you know, dependence and use disorders are two completely different things. And so sometimes I'll edit the diagnosis in my AMR to say F11.2 opioid dependence, physiologic only without opioid use disorder. I'll kind of tag that as a diagnosis, but this is, this can have significant implications, you know, late kind of labeling with a person with this diagnosis and that many people, when they look at that opioid dependence, their mind is going to go straight to addiction and assume that that person has a substance use disorder when they are not. And there's so much stigma related to that, that that can really kind of label a person and cause them to get, you know, I never do this without a patient's consent. If it's like a last ditch effort to get their insurance to pay for the medication, but not without their consent. This is just a slide from one of the addiction conferences, kind of saying to consideration of using long acting injectable buprenorphine for patients with pain, very kind of off label thing to do. But this large clinic that does that, this is their approach is using this F11.2 diagnosis. But there is no, no kind of studies. There's no information you're going to see out there about using extended release, long acting injectable buprenorphine, like sublocate for chronic pain. It is being done, but there's not really any literature on it yet. Uh, so this is one of our challenges and it makes everyone a little uncomfortable is that there is no MME conversion factor for buprenorphine to convert to other opioids. Okay. So you'll notice if you look at a PDMP report, the buprenorphine does not have an MME conversion. Any tables you see from reputable sources like the CDC, they never include buprenorphine. Um, there is no verified calculation. And the problem is it's not linear. It's a little bit like methadone in that way, but methadone for different reasons, but, but, um, the binding and the affinity and the activity, it's not a linear thing that you can just have one, you know, um, so, um, so, uh, you have to be a little creative and you have to do a little bit of trial and error to find the right dose that's going to work for that patient. Um, if you have a patient who is on lower doses, like less than 5,200 MME and their insurance covers the transdermal buccal forms, then go with that, you know, um, if the patient's willing and just follow the instructions that are in the product and it, and if it works for them, it works for them. That's great. Um, and if their insurance, um, um, does not cover these formulations or a patient is on, um, too high of doses to be able to qualify, to take those medications, then we're going to start with, um, uh, small doses of the sublingual tablets or films, um, like the two milligrams. So they come in two and milligram, two and eight milligram doses. So starting with the small ones that you can cut into little pieces. So you can start with as little as 0.5 milligrams and then be able to, um, plan to, um, uh, rapidly titrate up over the next couple of days as needed until you, um, do you get the appropriate amount of symptom control that the person needs? Let's talk something about the nuts and bolts of starting buprenorphine. We only have a couple of minutes. I'm sorry. You guys have to leave at eight 45. I think I'm going to go through some of those quickly precipitated withdrawal is if someone's on a really high dose of buprenorphine and of chronic opioids, and they take, um, kind of a low to medium dose of buprenorphine on the buprenorphine can knock all of the opiates off the receptor. And you go from full agonist to partial agonist, and you can get what's called precipitated withdrawal, where basically that very first dose of buprenorphine you take puts you into a draw and you feel sick until you get more buprenorphine on board. Um, this is treated by, um, by giving people more buprenorphine to get a higher level of opioid agonist, uh, happening. We don't actually see this happen very often at all in patients who are switching off from chronic opioid therapy, because we are able to plan out exactly. And we have time to plan out exactly how people to make the switch appropriately. There's two main initiation strategies, um, where the standards start where you have someone stop their opioids, um, waiting typically for like 12 hours after their last dose, sometimes longer, and then starting to take their buprenorphine versus this new approach of a low dose overlapping start where, um, they, um, we'll go over that. Um, you, um, when patients are stopping taking their buprenorphine, if they're on a really high dose of buprenorphine, what I tell them is, you know, um, stop taking your medication, wait for 12 hours at least. Um, and then just kind of wait as long as you can until you feel like I just can't wait anymore. I, you know, either I'm feeling sick with withdrawal symptoms or my pain is too bad. As long as you get past the 12 hour mark, you're going to, you're going to be fine. And then, um, and then they're going to, um, depending on their, um, dose, people are that, who are at, um, pretty lower MME doses. They can start with two milligram films, um, and just take, um, little pieces of that starting with like a quarter of them, repeating that dose every one to two hours as needed. Um, people who are on higher, you know, people are on maybe over a hundred MMEs. Um, they might also want to, um, uh, they could start with the eight milligram films and start with a quarter or one of those. So you're starting with, you know, two milligram doses and repeating those every, um, couple hours until you get the, um, effects. The medication, um, it has a quick onset of action. You're going to see the effect within 30 to six. Uh, it's going to start coming on 30 minutes and the peak effect in about 60 minutes after they take their dose of buprenorphine. Um, so the key is like really planning this out ahead of time. I'm not rushing into it, making sure that someone, um, like a case manager or nurse or an MA, someone is able to call and check in with that patient where you're having frequent follow-up telemedicine visits, um, a couple of days during that first week so that you can touch base and see how things are going. And if we may need to, um, change to a higher dose of medication, this is the low dose overlapping start. I'm not going to go into this because of time, but basically you, um, someone starts with, uh, who's on high doses of, uh, uh, uh, high MME, um, and doesn't want to stop before they start taking the buprenorphine. You can have them start out by taking, um, very, very small doses of buprenorphine and slowly ramping up at the same time that they're continuing to take their morphine or their oxycodone or whatever. Um, so, um, you're kind of overlapping those medications for about, um, four to seven days. Um, and then you don't have to go through that 12 to 24 hours of withdrawal in order to start the medication. Um, these are just an example of the kind of prescriptions I might write on a first visit as we're planning to make the switch over, um, uh, a small number of strips so that we can, um, rapidly titrate up to a different number, um, or a different dose. Um, and then I always give everyone Zofran because nausea is incredibly common side effect of buprenorphine. And if someone is worried about withdrawal symptoms, um, Clonidine I give to most people as well. And there's a number of other comfort medications, um, if people are, um, are going to be, um, or worried about experiencing withdrawal that you could prescribe. This medication, um, for opioid use disorder is sometimes dose once a day. Um, but really the, the pain relief, the analgesic effect is really short with buprenorphine. It only lasts about six to eight hours. So most patients are going to take their medication between two to four times a day, um, depending on what works for them and what they can do on a regular scheduled basis. It is a sublingual medication. So it's important to instruct people that sometimes they are tablets. People can get confused and swallow them. It is not absorbed GI it's destroyed by first pass metabolism. So, um, it has to be sublingual. Um, and then, um, after that 15, 20 minutes, they can rinse out and spit out, um, whatever is left in their mouth. They don't need to be swallowing this stuff. And it takes about five days of someone taking a dose to reach steady state. So I really encourage people that like that first week can be a little bumpy, um, you know, as, as the, the morphine or oxycodone, whatever is slowly coming out of your system. And we're waiting for the buprenorphine to reach steady state, um, you know, a week into it, or so you're probably gonna find that you have significantly better pain relief than you did like the first couple of days that you were taking the buprenorphine, but you're really, you know, going to check with them every week until their pain level, their dose, the withdrawal, any side effects is all stabilized. And the person is, is feeling stable. You know, so I check with everyone, you know, once a week for a couple of weeks and then every two weeks, and then we'll go to every month, just like we're going to monitor and refill this medication, just like we would for any other chronic opioid therapy. And when someone does have acute pain, you can also can prescribe, you know, additional doses of buprenorphine to treat acute pain. I also have some patients with chronic pain that I will give them a certain number of PRN doses, you know, during the month or per day, um, of buprenorphine to take PRN for pain as well. Generally, we don't have to worry about, um, uh, buprenorphine blocking the effect of other opioids until they're taking more than eight milligrams a day. So, um, but if people are taking more than eight milligrams a day, and they're going to be having a surgery, it might be good to, um, talk with someone that has experience with buprenorphine about how to help manage that person's pain perioperatively. These are some resources that you can check out that, um, talk a little bit about the use of buprenorphine in chronic pain, some webinars and some articles that might be interesting to read. Um, this is my contact information. So if you want to reach out to me, if you have a complex case and you're not quite sure how to approach it, um, you can reach out to me and ANTHC is going to be having a formal program for that starting in September for, um, for consultations. Um, and we would appreciate it if you would fill out the survey link for, um, uh, today and, um, then, um, you can get your CMEs as well. I don't know if there are CMEs for this. Chelsea, you're up. I'll stop and take questions. I think we're about out of time. There are CMEs available. I will be sending out that information to, um, Marsha and Dr. Anders later today so that you can all go online and access those as well.

Dr. Sarah Spencer

addiction medicine specialist

buprenorphine

chronic pain

opioid agonists

pain management